Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revascularization (HASTIER) is a focused ancillary imaging study to the Intravascular Cooling in the Treatment of Stroke 2 (ICTuS 2) trial, an ongoing, NIH-funded project on the safety and efficacy of hypothermia combined with thrombolysis. The objective of HASTIER is to address established preclinical concerns that hypothermia impairs recanalization and reperfusion with standard thrombolytic treatment with intravenous (IV) tissue plasminogen activator (tPA) for acute ischemic stroke in humans. Our hypothesis is that hypothermia does not impair either recanalization (opening of the artery) or reperfusion (restoration of downstream flow) with thrombolysis. This prospective, ancillary study of 120 ICTuS 2 subjects with middle cerebral artery stroke over 2 years uses an innovative imaging approach with multimodal CT/MRI to seamlessly evaluate these distinct aspects of revascularization. The relative impact of recanalization (CTA/MRA from baseline to 36 hours in Specific Aim 1) and reperfusion (CT/MR perfusion from baseline to 36 hours and imaging correlates of reperfusion such as hemorrhage and infarct growth in Specific Aim 2) may be impossible to predict or decipher without imaging as proposed in this study. Hypothermia and thrombolysis each offer potential benefit to improve stroke outcome, yet the concern regarding impaired thrombolysis during hypothermia may impede further translation. HASTIER uses an experienced core lab and expertise from landmark stroke imaging trials to test hypothermic thrombolysis against established revascularization benchmarks. HASTIER outcomes in Specific Aims 1 and 2 will provide distinct, yet complementary data essential to future development of combined hypothermia and thrombolysis with IV tPA. HASTIER imaging outcomes for recanalization and reperfusion may be extremely valuable irrespective of ICTuS 2 results, identifying the mechanisms that drive neurological outcomes and advancing other studies of revascularization beyond hypothermic thrombolysis. The expertise and infrastructure for this short, focused study of concrete scientific objectives will enhance the NIH investment in ICTuS 2, expanding knowledge on revascularization for acute stroke in humans and the impact of hypothermia. PUBLIC HEALTH RELEVANCE: Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revascularization (HASTIER) is an ancillary imaging study to the Intravascular Cooling in the Treatment of Stroke 2 (ICTuS 2) trial, an ongoing NIH-funded project on the safety and efficacy of hypothermia combined with thrombolysis. Understanding the beneficial effects and potential concerns of this combination treatment to open arteries and restore blood flow in stroke, the leading cause of adult disability in the US, is a key priority for improving pulic health. Imaging evaluation of revascularization will advance development of this combined approach and prominently impact other stroke treatments.